Small interfering RNAs (siRNAs) can turn off any specific gene in the genome. As a result, these molecules have tremendous potential as both scientific tools and therapeutics. However, delivering siRNA to the right cells in vivo has remained challenging. Using combinatorial chemical synthesis techniques and high-throughput biological screening methods, Daniel Anderson and co-workers have designed a nanoparticle that delivers siRNA to endothelial cells — cells that line blood and lymphatic vessels — at very low doses. Using this nanoparticle, the researchers turned off five genes at once inside an animal, turned off genes for more than three weeks after one injection, and reduced inflammation, tumour growth and metastasis. The cover image shows blood vessels in mouse adipose tissue stained with two endothelial cell markers, CD31 (blue) and ICAM-2 (magenta).

The ability to learn and remember previously encountered pathogens is a hallmark of the vertebrate immune system. CD8+ T cells, called central memory cells (TCM), mediate much more rapid and vigorous immune responses against the viruses that they recognize compared to their uneducated precursors, the naive T cells (TN). In this issue, Sung et al. (pp. 1249–1263) compare, at the single-cell level, the response of TN and TCM to a subcutaneous viral challenge. The invading virions are rapidly transported to the draining lymph nodes, where they infect macrophages that line the periphery of these bean-shaped organs. The image shows a cross-section of a lymph node in which virus-infected macrophages are identified by their yellow-green color. Initially, both TN and TCM reside in the deep T cell area (the dark region in the center of the organ). TCM, unlike TN, expresses CXCR3, a chemokine receptor that enables TCM to sense distant viral infections and to migrate peripherally between the B cell follicles (red) and into the medulla (the blue-green region on the left). This chemokine-dependent redistribution of TCM provides rapid access to viral antigen, which is critical for expedient clearance of the virus and, thus, represents a key molecular feature of immunological memory.

Section through a bone marrow cavity in the skull of a live mouse. The blood plasma is labelled with FITC-dextran (green). Note the rapid blood flow in the vessel center in the upper portion of the vessel. Rhodamine 6G (red) stains nuclei and mitochondria in the hematopoietic cells that adhere within the vessel (the round spheres insides the green detran-filled vessel) and the surrounding tissue. The cavity is enclosed in solid bone, which is not penetrated by rhodamine 6G and, hence, appears black.